The present invention relates to new triiodoisophthalic acid derivatives useful as opaque agents in x-ray contrast media.
For the complete roentgenological visualization of, for example, essential portions of the vascular system for instance, the aorta, or for the complete representation of the urinary tract system, contrast agent solutions must be administered in high concentrations to obtain satisfactory contrast in the system to be examined. Such high contrast medium concentrations, in turn, require that the contrast agents possess a very high water solubility with simultaneously low toxicity and good compatibility.
It is known that the general compatibility of x-ray contrast media depends on their hydrophilic character (P. K. Knoefel, Radiocontrast Agents, Vol. Pergamon Press [1971]: 133 et seq.). Moreover, it is known that the electrical charge of the cation and anion contributes substantially to a reduction of the lipophilic-toxic effects, expecially of the triiodinated aromatics.
In the presently used x-ray contrast medium salt solutions, the anion is the iodine-containing, opaquing components. The cation does not play any role in the forming of the x-ray radiographs. On the contrary, a number of undesirable effects ensue from their presence.
For example, all ions contribute toward the osmotic pressure of the x-ray contrast medium salt solutions in proportion to their molar concentrations, e.g., in the salts of substituted triiodobenzoic acids, half of the osmotic pressure originates from the iodine-free and thus contrast-ineffectual cation. The high osmotic pressure of concentrated x-ray contrast medium solutions is responsible for a number of undesirable pharmacological effects, such as vasodilation, pain, as well as a diuretic effect and thus a dilution of the excreted contrast medium in urography. Furthermore, the customary cations derived from iodine-free bases of high molecular weight, such as, meglumine, glucamine, lysine, arginine, and others, considerably raise the viscosity of the contrast medium solutions.
Cations having a lower molecular weight increase the viscosity of the contrast medium solutions to only a slight extent, but, on the other hand, have a toxic effect. Thus, it is known that there is damage to the blood-brain barrier and triggering of vascular pain by Na.sup.+ ions, and a higher toxicity of ethanolamine (EVILL, C. A. and G. T. BENNESS: Metrizamide as a Non-Ionic Urographic Agent, A Comparison with Sodium Iothalamate and Its Dimer, Invest. Radiol. 9: 434-437 [1974]; S. I. HILAL: Trends in Preparation of New Angiographic Contrast Media with Special Emphasis on Polymeric Derivatives, Invest. Radiol. 5: 458-468 [1970]).